title: Anti-HIV activity of human defensin 5 in primary CD4+ T cells under serum-deprived conditions is a consequence of defensin-mediated cytotoxicity.
abstract: BACKGROUND
  We have previously shown that human defensin 5 (HD5) promotes HIV infectivity in both primary CD4+ T cells and HeLa cells expressing CD4 and CCR5. HD5 is induced in response to sexually transmitted infections (STIs) such as Chlamydia trachomatis and Neisseria gonorrhoeae, suggesting it plays a role in STI-mediated enhancement of HIV transmission. In contrast to our findings, a recent study reports that HD5 has an anti-HIV effect in primary CD4+ T cells under serum-deprived conditions. To resolve these apparently contradictory observations, we investigated experimental parameters that might contribute to contrasting effects of HD5.
  
  
  RESULTS
  Serum-deprived culture conditions were associated with anti-HIV activity. In contrast to the dependence of the HIV enhancing effect on HD5 structure, the anti-HIV activity in serum-deprived primary CD4+ T cells was independent of HD5 structure as the linear peptide [Abu] HD5 exhibited similar anti-HIV activity. Under serum deprived conditions, HD5 blocked CD4-receptor-independent HIV-1vsv infection before or after viral entry. We found that HD5 and its linear form induced significant cell death in primary CD4+ T cells under serum-deprived culture conditions. HD5-mediated apoptosis was observed as early as 2 h after addition of defensins to serum-deprived primary CD4+ T cells. In contrast to primary CD4+ T cells, HD5 did not induce cytotoxicity and promote HIV infectivity of HeLa-CD4-CCR5 cells under serum-deprived conditions.
  
  
  CONCLUSIONS
  These results indicate that under serum-deprived culture conditions HD5 is toxic for primary CD4+ T cells, warranting caution in data interpretation.
authors.affiliation: Public Health Research Institute, Rutgers Biomedical and Health Sciences-New Jersey Medical School, Newark, New Jersey, United States of America.
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Carley
authors.initials: C
authors.lastname: Tasker
authors.forename: Kimyata
authors.initials: K
authors.lastname: Valere
authors.forename: Tiina
authors.initials: T
authors.lastname: Sihvonen
authors.forename: Dante B
authors.initials: DB
authors.lastname: Descalzi-Montoya
authors.forename: Wuyuan
authors.initials: W
authors.lastname: Lu
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Chang
mesh_terms: D017209:Apoptosis / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018929:Cell Culture Techniques; D016895:Culture Media, Serum-Free; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology / Q000635:transmission*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D023084:alpha-Defensins / Q000276:immunology* / Q000378:metabolism
chemical_list: D016895:Culture Media, Serum-Free; C500225:DEFA5 protein, human; D023084:alpha-Defensins